REVIEW PAPER
Genetic factors influencing HIV infection: a review
 
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Department of Infectious, Tropical Diseases and Immune Deficiency, Pomeranian Medical University in Szczecin, Szczecin, Poland
 
 
Submission date: 2021-12-01
 
 
Acceptance date: 2022-02-18
 
 
Publication date: 2022-11-20
 
 
HIV & AIDS Review 2023;22(1):1-5
 
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ABSTRACT
Patient’s genetic background, especially in the HLA and CCR5 regions, strongly influences outcomes of HIV-1 infection. Understanding how host genetic factors can contribute to disease progression can help guide intervention strategies. To date, it has been estimated that HLA and CCR5 loci account for around 13% of variations in viremia set point. However, a key question in understanding all complex phenotypes, including HIV-1 progression, is what degree of influence different genetic variants can have.
Presence of a 32bp deletion in CCR5 gene is associated with slower progression of HIV infection and positive effect on survival among cART untreated patients. Some studies have assessed CCR5-Δ32 as the most potent protective variant, both in immunological and viremic context, unrelated to HLA. Variants of CCR2 (rs1799864) are associated with slower progression to AIDS. CX3CR1 variant (rs3732378) may limit the shift in HIV-1 tropism from R5 to X4. This polymorphism may influence both disease progression and HIV tropism. HLA-C -35 (rs9264942) C/C variant is associated with a significant reduction in HIV viral load compared to T/T homozygote. Moreover, HLA-B*5701 has been confirmed to be more common in patients with slow disease progression to AIDS.
Patient’s genetic background, especially in HLA and CCR5 regions, strongly influences the progression of HIV-1 infection as well as viremic and immunologic values.
REFERENCES (49)
1.
German Advisory Committee Blood (Arbeitskreis Blut), Subgroup ‘Assessment of Pathogens Transmissible by Blood’. Human immunodeficiency virus (HIV). Transfus Med Hemother 2016; 43: 203-222.
 
2.
Oxford JS, Collier LH, Kellam P. Human Virology. Oxford University Press, Oxford 2016. Available from: https://books.google.pl/books?... (Accessed: 12.01.2020).
 
3.
Campbell EM, Hope TJ. HIV-1 capsid: the multifaceted key player in HIV-1 infection. Nat Rev Microbiol 2015; 13: 471-483.
 
4.
Maartens G, Celum C, Lewin SR. HIV infection: epidemiology, pathogenesis, treatment, and prevention. Lancet 2014; 384: 258-271.
 
5.
de Goede AL, Vulto AG, Osterhaus ADME, Gruters RA. Understanding HIV infection for the design of a therapeutic vaccine. Part I: Epidemiology and pathogenesis of HIV infection. Ann Pharm Fr 2015; 73: 87-99.
 
6.
Chereshnev VA, Bocharov G, Bazhan S, et al. Pathogenesis and treatment of HIV infection: the cellular, the immune system and the neuroendocrine systems perspective. Int Rev Immunol 2013; 32: 282-306.
 
7.
Mao Y, Wang L, Gu C, et al. Subunit organization of the membrane-bound HIV-1 envelope glycoprotein trimer. Nat Struct Mol Biol 2012; 19: 893-899.
 
8.
Rossi E, Meuser ME, Cunanan CJ, Cocklin S. Structure, function, and interactions of the hiv-1 capsid protein. Life (Basel) 2021; 11: 100.
 
9.
Shaw GM, Hunter E. HIV transmission. Cold Spring Harb Perspect Med 2012; 2: a006965.
 
10.
Fiebig EW, Wright DJ, Rawal BD, et al. Dynamics of HIV viremia and antibody seroconversion in plasma donors: implications for diagnosis and staging of primary HIV infection. AIDS 2003; 17: 1871-1879.
 
11.
Sabin CA, Lundgren JD. The natural history of HIV infection. Curr Opin HIV AIDS 2013; 8: 311-317.
 
12.
Okulicz JF, Marconi VC, Landrum ML, et al. Clinical outcomes of elite controllers, viremic controllers, and long-term nonprogressors in the US department of defense HIV natural history study. J Infect Dis 2009; 200: 1714-1723.
 
13.
Fellay J, Ge D, Shianna KV, et al. Common genetic variation and the control of HIV-1 in humans. PLoS Genet 2009; 5: e1000791.
 
14.
McLaren PJ, Carrington M. The impact of host genetic variation on infection with HIV-1. Nat Immunol 2015; 16: 577-583.
 
15.
Martin MP. Genetic acceleration of AIDS progression by a promoter variant of CCR5. Science 1998; 282: 1907-1911.
 
16.
Mummidi S, Ahuja SS, Gonzalez E, et al. Genealogy of the CCR5 locus and chemokine system gene variants associated with altered rates of HIV-1 disease progression. Nat Med 1998; 4: 786-793.
 
17.
Samson M, Libert F, Doranz BJ, et al. Resistance to HIV-1 infection in Caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature 1996; 382: 722-725.
 
18.
Sabeti PC, Walsh E, Schaffner SF, et al. The case for selection at CCR5-Δ32. PLoS Biol 2005; 3: e378.
 
19.
Parczewski M, Bander D, Leszczyszyn-Pynka M, et al. Risk of all-cause mortality in HIV infected patients is associated with clinical, immunologic predictors and the CCR5 Δ32 deletion. PLoS One 2011; 6: e22215.
 
20.
Ioannidis JPA, Contopoulos-Ioannidis DG, Rosenberg PS, et al. Effects of CCR5-delta32 and CCR2-64I alleles on disease progression of perinatally HIV-1-infected children: an international meta-analysis. AIDS 2003; 17: 1631-1638.
 
21.
Knudsen TB, Kristiansen TB, Katzenstein TL, Eugen-Olsen J. Adverse effect of the CCR5 promoter −2459A allele on HIV-1 disease progression. J Med Virol 2001; 65: 441-444.
 
22.
Gorelick PB. Role of inflammation in cognitive impairment: results of observational epidemiological studies and clinical trials. Ann N Y Acad Sci 2010; 1207: 155-162.
 
23.
Bolus WR, Gutierrez DA, Kennedy AJ, Anderson-Baucum EK, Hasty AH. CCR2 deficiency leads to increased eosinophils, alternative macrophage activation, and type 2 cytokine expression in adipose tissue. J Leukoc Biol 2015; 98: 467-477.
 
24.
Singh KK, Barroga CF, Hughes MD, et al. Genetic influence of CCR5, CCR2, and SDF1 variants on human immunodeficiency virus 1 (HIV-1)-related disease progression and neurological impairment, in children with symptomatic HIV-1 infection. J Infect Dis 2003; 188: 1461-1472.
 
25.
Combadiere C, Salzwedel K, Smith ED, Tiffany HL, Berger EA, Murphy PM. Identification of CX3CR1. A chemotactic receptor for the human CX3C chemokine fractalkine and a fusion coreceptor for HIV-1. J Biol Chem 1998; 273: 23799-23804.
 
26.
CX3CR1 C-X3-C motif chemokine receptor 1 [Homo sapiens (human)] – Gene – NCBI. Available from: https://www.ncbi.nlm.nih.gov/g... (Accessed: 04.12.2020).
 
27.
Parczewski M, Urbańska A, Maciejewska K, Clark J, Leszczyszyn-Pynka M. Association of chemokine receptor gene variants with HIV-1 genotype predicted tropism. HIV Med 2014; 15: 577-586.
 
28.
Leszczyszyn-Pynka M, Aksak-Was B, Urbańska A, Parczewski M. Protective effect of HLA-B*5701 and HLA-C-35 genetic variants in HIV-positive Caucasians from Northern Poland. PLoS One 2015; 10: e0127867.
 
29.
Fellay J, Shianna KV, Ge D, et al. A whole-genome association study of major determinants for host control of HIV-1. Science 2007; 317: 944-947.
 
30.
Blais ME, Dong T, Rowland-Jones S. HLA-C as a mediator of natural killer and T-cell activation: spectator or key player? Immunology 2011; 133: 1-7.
 
31.
Alter G, Altfeld M. NK cells in HIV-1 infection: evidence for their role in the control of HIV-1 infection. J Intern Med 2009; 265: 29-42.
 
32.
Blais ME, Zhang Y, Rostron T, et al. High frequency of HIV mutations associated with HLA-C suggests enhanced HLA-C-restricted CTL selective pressure associated with an AIDS-protective polymorphism. J Immunol 2012; 188: 4663-4670.
 
33.
Tiemessen CT, Paximadis M, Minevich G, et al. Natural killer cell responses to HIV-1 peptides are associated with more activating KIR genes and HLA-C genes of the C1 allotype. J Acquir Immune Def Syndr 2011; 57: 181-189.
 
34.
Suppiah V, Gaudieri S, Armstrong NJ, et al. IL28B, HLA-C, and KIR variants additively predict response to therapy in chronic hepatitis C virus infection in a European cohort: a cross-sectional study. PLoS Med 2011; 8: e1001092.
 
35.
Elahi S, Horton H. Association of HLA-alleles with the immune regulation of chronic viral infections. Int J Biochem Cell Biol 2012; 44: 1361-1365.
 
36.
Venkataramana NK, Kumar SKV, Balaraju S, et al. Open-labeled study of unilateral autologous bone-marrow-derived mesenchymal stem cell transplantation in Parkinson’s disease. Transl Res 2010; 155: 62-70.
 
37.
Majorczyk E, Matusiak Ł, Nowak I, et al. A single nucleotide polymorphism -35kb T > C (rs9264942) is strongly associated with psoriasis vulgaris depending on HLA-Cw*06. Hum Immunol 2014; 75: 504-507.
 
38.
Saag M, Balu R, Phillips E, et al. High sensitivity of human leukocyte antigen-B*5701 as a marker for immunologically confirmed abacavir hypersensitivity in white and black patients. Clin Infect Dis 2008; 46: 1111-1118.
 
39.
Orkin C, Wang J, Bergin C, et al. An epidemiologic study to determine the prevalence of the HLA-B*5701 allele among HIV-positive patients in Europe. Pharmacogenet Genomics 2010; 20: 307-314.
 
40.
Parczewski M, Leszczyszyn-Pynka M, Wnuk A, et al. Introduction of pharmacogenetic screening for the human leucocyte antigen (HLA) B*5701 variant in Polish HIV-infected patients. HIV Med 2010; 11: 345-348.
 
41.
Gao X, O’Brien TR, Welzel TM, et al. HLA-B alleles associate consistently with HIV heterosexual transmission, viral load, and progression to AIDS, but not susceptibility to infection. AIDS 2010; 24: 1835-1840.
 
42.
Migueles SA, Sabbaghian MS, Shupert WL, et al. HLA B*5701 is highly associated with restriction of virus replication in a subgroup of HIV-infected long term nonprogressors. Proc Natl Acad Sci U S A 2000; 97: 2709-2714.
 
43.
Carrington M, O’Brien SJ. The influence of HLA genotype on AIDS. Annu Rev Med 2003; 54: 535-551.
 
44.
Gillespie GMA, Kaul R, Dong T, et al. Cross-reactive cytotoxic T lymphocytes against a HIV-1 p24 epitope in slow progressors with B*57. AIDS 2002; 16: 961-972.
 
45.
Yu XG, Lichterfeld M, Chetty S, et al. Mutually exclusive T-cell receptor induction and differential susceptibility to human immunodeficiency virus type 1 mutational escape associated with a two-amino-acid difference between HLA class I subtypes. J Virol 2007; 81: 1619-1631.
 
46.
Zhao YE, Ma JX, Hu L, Xiao SX, Zhao YL. Meta-analysis of the association between psoriasis and human leucocyte antigen-B. Br J Dermatol 2013; 169: 417-427.
 
47.
Feng BJ, Sun LD, Soltani-Arabshahi R, et al. Multiple loci within the major histocompatibility complex confer risk of psoriasis. PLoS Genet 2009; 5: e1000606.
 
48.
Ho SS, McLachlan AJ, Chen TF, Hibbs DE, Fois RA. Relationships between pharmacovigilance, molecular, structural, and pathway data: revealing mechanisms for immune-mediated drug-induced liver injury. CPT Pharmacometrics Syst Pharmacol 2015; 4: 426-441.
 
49.
Salgado M, Simón A, Sanz-Minguela B, et al. An additive effect of protective host genetic factors correlates with HIV nonprogression status. J Acquir Immune Def Syndr 2011; 56: 300-305.
 
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